1. Academic Validation
  2. Collagen alpha-5(IV) chain activation by nuclear factor 1/C promotes nasopharyngeal carcinoma progression

Collagen alpha-5(IV) chain activation by nuclear factor 1/C promotes nasopharyngeal carcinoma progression

  • Hum Cell. 2025 Aug 20;38(5):148. doi: 10.1007/s13577-025-01278-9.
Ying Cao # 1 Peibei Wang # 2 Peng Li # 3 Kai Wei # 1 Xinle Kang 4 Xiao Han 5 De Huai 1 Bing Fei 6
Affiliations

Affiliations

  • 1 Department of Ear-Nose-Throat, The Second People's Hospital of Huai'an, Huai'an Affiliated Hospital of Xuzhou Medical University, No. 60, Huaihai South Road, Qingjiangpu District, Huai'an, 223000, Jiangsu, People's Republic of China.
  • 2 Department of Ear-Nose-Throat, Taizhou Second People's Hospital Affiliated to Yangzhou University, Taizhou, 225599, Jiangsu, People's Republic of China.
  • 3 Department of Radiation Oncology, Huai'an Hospital of Huai'an City, Huai'an, 223001, Jiangsu, People's Republic of China.
  • 4 Department of Ophthalmology, The Second People's Hospital of Huai'an, Huai'an Affiliated Hospital of Xuzhou Medical University, Huai'an, 223000, Jiangsu, People's Republic of China.
  • 5 Department of Pathology, Huai'an Hospital of Huai'an City, Huai'an, 223001, Jiangsu, People's Republic of China.
  • 6 Department of Ear-Nose-Throat, The Second People's Hospital of Huai'an, Huai'an Affiliated Hospital of Xuzhou Medical University, No. 60, Huaihai South Road, Qingjiangpu District, Huai'an, 223000, Jiangsu, People's Republic of China. feibing11178@126.com.
  • # Contributed equally.
Abstract

The expression of Collagen receptors by Cancer cells serves a vital function in the regulation of cell behavior. These receptors are capable of sensing the signals generated by alterations in the Collagen state, thereby contributing to the maintenance of cellular homeostasis. The Discoidin Domain Receptor (DDR)1 functions as a critical sensor of Collagen fiber state and composition, regulating tumor cell growth, response to therapy, and patient survival. We evaluated the role of Collagen alpha-5(IV) chain (COL4A5) in nasopharyngeal carcinoma (NPC) and the detailed mechanism. GSE118719 and GSE68799 datasets were included to identify COL4A5 as a hub gene in NPC. Transcriptional activation of COL4A5 by nuclear factor 1/C (NFIC) mediated DDR1/Akt signaling activation, promoted NPC cell proliferation, migration, invasion, and curbed Apoptosis in vitro, and exacerbated malignant progression of subcutaneous tumors in nude mice. NFIC and COL4A5 were significantly overexpressed in the tumors of NPC patients, and their expressions were significantly positively correlated. The overexpression of NFIC and COL4A5 was closely related to the tumor, node, metastases stage of NPC patients. Collectively, our results suggest that NFIC transcriptionally activates COL4A5 and upregulates its expression, which mediates DDR1/Akt signaling and promotes the malignant behavior of NPC cells, leading to NPC progression.

Keywords

Akt signaling; COL4A5; DDR1; NFIC; Nasopharyngeal carcinoma.

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